title: The fusion partner specifies the oncogenic potential of NUP98 fusion proteins.
abstract: NUP98 is among the most promiscuously translocated genes in hematological diseases. Among the 28 known fusion partners, there are two categories: homeobox genes and non-homeobox genes. The homeobox fusion partners are well-studied in animal models, resulting in HoxA cluster overexpression and hematological disease. The non-homeobox fusion partners are less well studied. We created transgenic animal models for three NUP98 fusion genes (one homeobox, two non-homeobox), and show that in this system, the NUP98-homeobox fusion promotes self-renewal and aberrant gene expression to a significantly greater extent. We conclude that homeobox partners create more potent NUP98 fusion oncogenes than do non-homeobox partners.
authors.affiliation: Division of Blood Cancers, Australian Centre for Blood Diseases, Central Clinical School, Monash University, Melbourne, VIC, Australia.
authors.forename: Jesslyn
authors.initials: J
authors.lastname: Saw
authors.forename: David J
authors.initials: DJ
authors.lastname: Curtis
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Hussey
authors.forename: Alexander
authors.initials: A
authors.lastname: Dobrovic
authors.forename: Peter D
authors.initials: PD
authors.lastname: Aplan
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Slape
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics; D004264:DNA Topoisomerases, Type I / Q000235:genetics; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000502:physiology*; D014178:Translocation, Genetic / Q000502:physiology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D020662:Guanine Nucleotide Exchange Factors; D018398:Homeodomain Proteins; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; C093350:nuclear pore complex protein 98; C100815:Kifap3 protein, mouse; D004264:DNA Topoisomerases, Type I
keywords: HOX; Homeobox; Leukemia; NUP98; Translocation